DOI: https://doi.org/10.18370/2309-4117.2018.39.8-14

Correction of hormonal imbalance in patients with diffuse forms of mastopathy – the basis of pathogenetic therapy and oncoprophylaxis

Н. В. Косей

Abstract


The physiological processes of cell division occurring in the tissues of the non-invading mammary gland (MG) are a response to the cyclic changes in the level of estrogens and progesterone released by the ovaries. Violation of the balance between estrogen and progesterone in women of reproductive age can cause dyshormonal hyperplasia of the mammary gland (DHMG). The cyclic form of mastalgia is dangerous not only for its manifestations, but also for the existence of a proven connection with an increased risk of breast cancer (BC).

In particular, in a large cohort study in France, it was shown that women who had suffered from cyclic mastalgia for more than 3 years and who had not received treatment had a 5-fold increased risk of breast cancer compared to women who did not have it. In 2016, a meta-analysis of the numerous studies was confirmed that the use of estrogen with micronized progesterone is associated with a lower risk of breast cancer compared with synthetic progestogens. It has been established that progesterone deficiency creates conditions for uncontrolled proliferation in MG tissues and promotes the development of Fibro-cystic disease (FCD).

The use of transdermal gel progesterone allows you to balance the excess effects of estrogens on MG, primarily eliminating the excess permeability of tissue capillaries, the mitotic activity of milk duct cells and the painful stretching of the MG tissue. Studies have shown that when using a gel with progesterone (Progestogel®), there is a decrease in mitotic activity in normal cells of the lobular epithelium of the MF. The antiproliferative effect of the Progestogel® is realized when it is used in a continuous mode – every day of the cycle, including the days of menstruation.

A retrospective study of the effectiveness of the use of Progestogel® in monotherapy with FCD showed that against a background of local therapy with gel with progesterone there was a statistically significant decrease and disappearance of mastalgia, mastodynia, decrease average size and number of cysts. Progestogel® with course treatment reduces the mammographic density of MG, which is also considered as an independent and extremely significant risk factor for breast cancer. The local application of the gel with progesterone makes it possible to avoid many unnecessary surgical operations to remove cysts.


Keywords


breast cancer; fibro-cystic disease; progesterone; Progestogel

References


Smolanka, I.I., Dosenko, I.V., Lyashchenko, A.A., et al. “Dyshormonal hyperplasia of the mammary glands: etiology, clinical forms, diagnostic algorithms, principles of therapy.” Consilium Medicum Ukraina 6 Vol.1 (2007): 11–8.

Ferguson, D.J. “An ultrastructural study of mitosis and cytokinesis in normal ‘resting’ human breast.” Cell Tissue Res 252 (1988): 581–7.

Desreux, J., et al. “Progesterone receptor activation: an alternative to SERMs in breast cancer.” Eur J Cancer 36 (2000): 90–91.

Malet, C., et al. “Progesterone effect on cell growth, ultrastructural aspect and estradiol receptors of normal human breast epithelial (HBE) cells in culture.” J Steroid Biochem Mol Biol 73 (2000): 171–81.

Hamoshina, M.B., Parenkova, I.A. Do not ignore mastopathy – do not tolerate cancer. New vector of tactics in mastopathy: active cancer prevention: Information letter / Ed. by V.E. Radzinsky, N.I. Rozhkova. Moscow. Editorial board of the Journal “StatusPraesens” (2016): 24 p.

Society of Obstetricians and Gynecologists of Canada (SOGC). “Mastalgia.” J Obstet Gynaecol Can 28.1 (2006): 49–71.

Millet, A.V., Dirbas, F.M. “Clinical management of breast pain: a review.” Obstet Gynecol Surv 57.7 (2002): 451–6.

Davies, E.L., Gateley, C.A., Miers, M., Mansel, R.E. “The long-term course of mastalgia.” J R Soc Med 91 (1998): 462–4.

Plu-Bureau, G., Lê, M.G., Sitruk-Ware, R., Thalabard, J.C. “Cyclical mastalgia and breast cancer risk: results of a French cohort study.” Cancer Epidemiol Biomarkers Prev 15.6 (2006): 1229–31.

Heldring, N., et al. “Estrogen receptors: how do they signal and what are their targets.” Physiol Rev 87 (2007): 905–31.

Clarke, C.L., Sutherland, R.L. “Progestin regulation of cellular proliferation.” Endocr Rev 11 (1990): 266–301.

Graham, J.D., Mote, P.A., Salagame, U., et al. “DNA Replication Licensing and Progenitor Numbers Are Increased by Progesterone in Normal Human Breast Endocrinology.” 150.7 (2009): 3318–26.

Sitruk-Ware, R., et al. “Inadequate corpus luteal function in women with benign breast diseases.” J Clin Endocrin Metab 1997; 44: 771.

Dyrstad, S.W., et al. “Breast cancer risk associated with benign breast disease: systematic review and meta-analysis.” Breast Cancer Res Treat 149.3 (2015): 569–75.

Bespalov, V.G., Travina, M.L. “Fibrocystic disease and breast cancer risk (literature review).” Tumors of female reproductive system 4.11 (2015): 58–70. DOI: 10.17 650 / 1994-4098-2015-11-4-58-70

Rossouw, J.E., Anderson, G.L., Prentice, R.L., et al. “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial.” JAMA 288 (2002): 321–33.

Stephenson, G.D., Rose, D.P. “Breast cancer and obesity: an update.” Nutr Cancer 45.1 (2003): 1–16.

Bernstein, L.M. Hormonal carcinogenesis. Sankt-Petersburg. Nauka (2000): 199 p.

Russo, J., Russo, J.H. “The role of estrogen in initiation of breast cancer.” J Steroid Biochem Mol Biol 102.1–5 (2006): 89–96.

Arnav Katira, Peng H. Tan. “Evolving role of adiponectin in cancer-controversies and update.“ Cancer Biol Med 13.1 (2016): 101–9.

Divella, R., De Luca, R., Abbate, I., et al. “Obesity and cancer: the role of adipose tissue and adipo-cytokinesinduced chronic inflammation.“ J Cancer 7.15 (2017): 2346–59. DOI: 10.7150/jca.16884

Fournier, A., Berrino, F., Clavel-Chapelon, F. “Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study.” Breast Cancer Res Treat 107.1 (2008): 103–11.

Wood, C.E., Register, T.C., Lees, C.J., et al. “Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys.” Breast Cancer Res Treat 101.2 (2007): 125–34.

Wood, C.E., Register, T.C., Cline, J.M. “Transcriptional profiles of progestogen effects in the postmenopausal breast.” Breast Cancer Res Treat 114.2 (2009): 233–42.

Murkes, D., Conner, P., Leifland, K., et al. “Effects of estrogens-medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy women.” Fertil Steril 95.3 (2011): 1188–91.

Noor Asi, Khaled Mohammed, Qusay Haydour, et al. “Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis.” Syst Rev 5 (2016): 121–9.

Shabalova, I.P., Dzhangirova, T.V., Volchenko, N.N., Pugachev, K.K. Cytological atlas: diagnosis of breast diseases. Moscow-Tver. Triada (2005).

Korzhenkova, G.P. “Diagnostic value of BI-RADS categories in the management of patients with benign breast pathology.” Tumors of female reproductive system 12.4 (2016): 10–6.

Smetnik, V.P. “Sex hormones and mammary gland (review of literature).” Gynecology 2.5 (2000): 133–6.

Barrat, J., Lignieres, B., de Mаrpeau, L., et al. “The in vivo effect of the local administration of progesterone on the mitotic activity of human ductal breast tissue. Results of a pilot study.” J Gynecol Obstet Biol Reprod 19.3 (1990): 269–74.

Brkic, M., et al. “The Influence of Progesterone Gel Therapy in the Treatment of Fibrocystic Breast Disease.“ Open Journal of Obstetrics and Gynecology 6 (2016): 334–41.

Bespalov, V.G., Negustov, Y.F. “Mammographic density as a criterion for the effectiveness of treatment of mastopathy and reducing the risk of breast cancer.” Tumors of female reproductive system 13.2 (2017): 33–41.


GOST Style Citations


1. Смоланка, И.И. Дисгормональные гиперплазии молочных желез: этиология, клинические формы, алгоритмы диагностики, принципы терапии / И.И. Смоланка, И.В. Досенко, А.А. Лященко и др. // Consilium Medicum Ukraina. – 2007. – Т. 1, № 6. –С. 11–18.

2. Ferguson, D.J. “An ultrastructural study of mitosis and cytokinesis in normal ‘resting’ human breast.” Cell Tissue Res 252 (1988): 581–7.

3. Desreux, J., et al. “Progesterone receptor activation: an alternative to SERMs in breast cancer.” Eur J Cancer 36 (2000): 90–91.

4. Malet, C., et al. “Progesterone effect on cell growth, ultrastructural aspect and estradiol receptors of normal human breast epithelial (HBE) cells in culture.” J Steroid Biochem Mol Biol 73 (2000): 171–81.

5. Hamoshina, M.B., Parenkova, I.A. Do not ignore mastopathy – do not tolerate cancer. New vector of tactics in mastopathy: active cancer prevention: Information letter / Ed. by V.E. Radzinsky, N.I. Rozhkova. Moscow. Editorial board of the Journal “StatusPraesens” (2016): 24 p.

6. Society of Obstetricians and Gynecologists of Canada (SOGC). “Mastalgia.” J Obstet Gynaecol Can 28.1 (2006): 49–71.

7. Millet, A.V., Dirbas, F.M. “Clinical management of breast pain: a review.” Obstet Gynecol Surv 57.7 (2002): 451–6.

8. Davies, E.L., Gateley, C.A., Miers, M., Mansel, R.E. “The long-term course of mastalgia.” J R Soc Med 91 (1998): 462–4.

9. Plu-Bureau, G., Lê, M.G., Sitruk-Ware, R., Thalabard, J.C. “Cyclical mastalgia and breast cancer risk: results of a French cohort study.” Cancer Epidemiol Biomarkers Prev 15.6 (2006): 1229–31.

10. Heldring, N., et al. “Estrogen receptors: how do they signal and what are their targets.” Physiol Rev 87 (2007): 905–31.

11. Clarke, C.L., Sutherland, R.L. “Progestin regulation of cellular proliferation.” Endocr Rev 11 (1990): 266–301.

12. Graham, J.D., Mote, P.A., Salagame, U., et al. “DNA Replication Licensing and Progenitor Numbers Are Increased by Progesterone in Normal Human Breast Endocrinology.” 150.7 (2009): 3318–26.

13. Sitruk-Ware, R., et al. “Inadequate corpus luteal function in women with benign breast diseases.” J Clin Endocrin Metab 1997; 44: 771.

14. Dyrstad, S.W., et al. “Breast cancer risk associated with benign breast disease: systematic review and meta-analysis.” Breast Cancer Res Treat 149.3 (2015): 569–75.

15. Беспалов, В.Г. Фиброзно-кистозная болезнь и риск рака молочной железы (обзор литературы) / В.Г. Беспалов, М.Л. Травина // Опухоли женской репродуктивной системы. – 2015. – № 4 (11). – С. 58–70.

16. Rossouw, J.E., Anderson, G.L., Prentice, R.L., et al. “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial.” JAMA 288 (2002): 321–33.

17. Stephenson, G.D., Rose, D.P. “Breast cancer and obesity: an update.” Nutr Cancer 45.1 (2003): 1–16.

18. Бернштейн, Л.М. Гормональный канцерогенез / Л.М.Бернштейн – СПб.: Наука, 2000. – 199 с.

19. Russo, J., Russo, J.H. “The role of estrogen in initiation of breast cancer.” J Steroid Biochem Mol Biol 102.1–5 (2006): 89–96.

20. Arnav Katira, Peng H. Tan. “Evolving role of adiponectin in cancer-controversies and update.“ Cancer Biol Med 13.1 (2016): 101–9.

21. Divella, R., De Luca, R., Abbate, I., et al. “Obesity and cancer: the role of adipose tissue and adipo-cytokinesinduced chronic inflammation.“ J Cancer 7.15 (2017): 2346–59. DOI: 10.7150/jca.16884

22. Fournier, A., Berrino, F., Clavel-Chapelon, F. “Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study.” Breast Cancer Res Treat 107.1 (2008): 103–11.

23. Wood, C.E., Register, T.C., Lees, C.J., et al. “Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys.” Breast Cancer Res Treat 101.2 (2007): 125–34.

24. Wood, C.E., Register, T.C., Cline, J.M. “Transcriptional profiles of progestogen effects in the postmenopausal breast.” Breast Cancer Res Treat 114.2 (2009): 233–42.

25. Murkes, D., Conner, P., Leifland, K., et al. “Effects of estrogens-medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy women.” Fertil Steril 95.3 (2011): 1188–91.

26. Noor Asi, Khaled Mohammed, Qusay Haydour, et al. “Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis.” Syst Rev 5 (2016): 121–9.

27. Шабалова, И.П., Джангирова, Т.В., Волченко, Н.Н., Пугачев, К.К. Цитологический атлас: диагностика заболеваний молочной железы. – М.-Тверь: Триада, 2005.

28. Корженкова, Г.П. Диагностическое значение категорий BI-RADS в ведении пациенток с доброкачественной патологией молочных желез / Г.П. Корженкова // Опухоли женской репродуктивной системы. – 2016. – Т. 12, №4. – С. 10–16.

29. Сметник, В.П. Половые гормоны и молочная железа (обзор литературы) / В.П. Сметник //Гинекология. – 2000. – Т.2, №5. – С. 133–136.

30. Barrat, J., Lignieres, B., de Mаrpeau, L., et al. “The in vivo effect of the local administration of progesterone on the mitotic activity of human ductal breast tissue. Results of a pilot study.” J Gynecol Obstet Biol Reprod 19.3 (1990): 269–74.

31. Brkic, M., et al. “The Influence of Progesterone Gel Therapy in the Treatment of Fibrocystic Breast Disease.“ Open Journal of Obstetrics and Gynecology 6 (2016): 334–41.

32. Беспалов, В.Г. Маммографическая плотность как критерий эффективности лечения мастопатии и снижения риска рака молочной железы / В.Г. Беспалов, Ю.Ф. Негустов // Опухоли женской репродуктивной системы. – 2017. – Т. 13, №2. – С. 33–41.





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